DESCRIPTION: Our previous work has demonstrated that the vestibular system has strong influences on muscles that reduce respiration, including the diaphragm, abdominal muscles (the major expiratory muscles), and muscles at regulate the resistance of the upper airway. All of the respiratory outflows examined so far are most powerfully influenced by pitch rotations that activate otolith organs, with nose-up tilt increasing respiratory muscle activity. Nose-up tilt in quadrupeds also challenges breathing, suggesting that vestibulo-respiratory reflexes are important for maintaining stable ventilation during changes in posture. Presumably, deficits in vestibulo-respiratory responses would lead to unstable blood oxygenation during postural changes, as occurs in medical conditions such as obstructive sleep apnea. Our work has also shown that brainstem neurons in addition to those that generate the respiratory cycle relay vestibular signals to respiratory motoneurons. In this way, vestibulo-respiratory reflexes are similar to vomiting, which also involves contraction of respiratory muscles that is elicited in part by neurons outside the major brainstem respiratory groups. A common pool of brainstem neurons may mediate both responses. The aims of this renewal application fall into two groups. In the first two aims, we will further characterize the properties of vestibulo-respiratory reflexes in both decerebrate and awake animals, to provide a better appreciation of the physiological significance of these responses. We will examine how inputs from neck and vestibular receptors are integrated by respiratory pathways, and will test the hypothesis that vestibulo-respiratory reflexes have similar characteristics in awake animals as in decerebrate preparations. In the second group of specific aims, we will determine the neural pathways that relay vestibular signals to respiratory motoneurons. We will use neuroanatomical techniques to determine the locations of neurons outside of the major respiratory groups that project to respiratory motoneurons, and will analyze the responses of these neurons to vestibular stimulation. Knowledge about vestibular influences on respiratory muscles will be compared to existing information about other vestibulo-spinal reflexes, which may lead to new insights about the role of vestibular signals in motor control. In addition, these experiments will reveal the possible medical consequences of deficiencies in vestibulo-respiratory reflexes, and will provide evidence that will be important in providing treatments for these conditions. Thus, the proposed experiments have both scientific and potential clinical value.